Numerical matching during cerebellar development: quantitative analysis of granule cell death in staggerer mouse...

Cell death is a common yet puzzling feature of the development of many populations of neurons in the CNS. In the invertebrate phyla, such death is often preprogrammed; by contrast, in vertebrates, the best studied examples of histogenetic cell death are influenced by interactions among the neurons and their target. One attempt to explain this seemingly wasteful scheme of development has led to the hypothesis that this target-related cell death allows 2 populations of cells, which develop in isolation, to come into numerical and functional balance and hence to provide an epigenetic "buffer" mechanism to accommodate developmental variations. In the current study we have examined the extent to which the cell death observed in the cerebellar granule cell population serves to numerically match these neurons with their primary postsynaptic target, the Purkinje cell. Staggerer chimeras were made by aggregating 8-cell staggerer embryos with embryos of wild-type genotype. The cerebella of the resulting animals developed with widely varying numbers of normal (wild-type) Purkinje cell targets. Although staggerer Purkinje cells were present in the chimeric brains, these cells are intrinsically deficient in their normal developmental program (in the mutant, because of this deficiency, 100% of the granule cells die). Both granule cells and Purkinje cells were counted in chimeras and several wild-type mice. The results reveal that the number of granule cells present in these brains has a linear relationship with the number of Purkinje cells, and that the line connecting the points intersects the Y-axis close to the origin. These observations suggest that numerical matching is an important function of target-related cell death in the granule cell population.(ABSTRACT TRUNCATED AT 250 WORDS)